Disparities in HPV Vaccination Among Adolescents by Health Care Facility Type.

Importance: Approximately 31 000 cases of human papillomavirus (HPV)-associated cancers are diagnosed annually in the US. The HPV vaccine can prevent more than 90% of these cancers, yet national uptake remains lower than the Healthy People 2030 target of 80% completion. To devise targeted interventions to increase the uptake of HPV vaccines, it is crucial to understand the vaccination rates across various health care settings. Objective: To examine the association between health care facility type and adolescent HPV vaccine uptake and clinician recommendation for the vaccine in the US. Design, Setting, and Participants: This cross-sectional study uses a complex sampling design of data from the 2020 National Immunization Survey-Teen. The study included adolescents aged 13 to 17 years. The data analysis was completed between March 1 and May 31, 2022. Exposure: Health care facility type classified as public, hospital-based, private, mixed (more than 1 type), and other facilities (eg, military health care facility; Women, Infants, and Children clinic; school-based health center; pharmacy). Main Outcomes and Measures: Initiation of HPV vaccination was defined as the receipt of at least 1 dose of the HPV vaccine and completion as receipt of at least 2 or 3 doses, depending on age of initiation. Parent or guardian self-reported clinician recommendation was categorized as yes or no. Weighted, multivariable logistic regression models were used to estimate the odds of initiating and completing the HPV vaccine series and receiving clinician recommendation by health care facility type adjusted for adolescent and maternal characteristics. Results: A total of 20 162 adolescents (mean [SD] age, 14.9 [1.4] years; 51.0% male) were included. Clinician recommendation for the HPV vaccine was received by 81.4% of adolescents, and 75.1% initiated and 58.6% completed the HPV vaccine series. In the adjusted analyses, adolescents who received recommended vaccinations at public facilities had lower odds of initiating (adjusted odds ratio [AOR], 0.71; 95% CI, 0.58-0.88) and completing (AOR, 0.62; 95% CI, 0.51-0.76) HPV vaccination compared with those who received recommended vaccinations at private facilities. Similarly, adolescents who received recommended vaccinations at public facilities (AOR, 0.62; 95% CI, 0.51-0.77) had lower odds of receiving a clinician recommendation for the HPV vaccine compared with those who received recommended vaccinations at private facilities. Conclusions and Relevance: These findings reveal health disparities in HPV vaccination among adolescent populations served by public health care facilities, suggesting that a greater focus is needed on vaccine recommendations and uptake in public facilities.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Trends in Reasons for Human Papillomavirus Vaccine Hesitancy: 2010-2020.

OBJECTIVES: We sought to identify trends in the main reasons United States parents of unvaccinated children gave for not intending to vaccinate their adolescent children against HPV from 2010 to 2020. As interventions designed to increase vaccine uptake have been implemented across the United States, we predicted that reasons for hesitancy have changed over this period. METHODS: We analyzed data from the 2010 to 2020 National Immunization Survey-Teen, which included 119 695 adolescents aged 13 to 17 years. Joinpoint regression estimated yearly changes in the top five cited reasons for not intending to vaccinate using annual percentage changes. RESULTS: The five most frequently cited reasons for not intending to vaccinate included "not necessary," "safety concerns," "lack of recommendation," "lack of knowledge," and "not sexually active." Overall, parental HPV vaccine hesitancy decreased by 5.5% annually between 2010 and 2012 and then remained stable for the 9-year period of 2012 through 2020. The proportion of parents citing "safety or side effects" as a reason for vaccine hesitancy increased significantly by 15.6% annually from 2010 to 2018. The proportion of parents citing "not recommended," "lack of knowledge," or "child not sexually active" as reasons for vaccine hesitancy decreased significantly by 6.8%, 9.9%, and 5.9% respectively per year between 2013 and 2020. No significant changes were observed for parents citing "not necessary." CONCLUSIONS: Parents who cited vaccine safety as a reason for not intending to vaccinate their adolescent children against HPV increased over time. Findings support efforts to address parental safety concerns surrounding HPV vaccination.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium.

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Disrupted PI3K subunit p110α signaling protects against pulmonary hypertension and reverses established disease in rodents.

Enhanced signaling via RTKs in pulmonary hypertension (PH) impedes current treatment options because it perpetuates proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Here, we demonstrated hyperphosphorylation of multiple RTKs in diseased human vessels and increased activation of their common downstream effector phosphatidylinositol 3'-kinase (PI3K), which thus emerged as an attractive therapeutic target. Systematic characterization of class IA catalytic PI3K isoforms identified p110α as the key regulator of pathogenic signaling pathways and PASMC responses (proliferation, migration, survival) downstream of multiple RTKs. Smooth muscle cell-specific genetic ablation or pharmacological inhibition of p110α prevented onset and progression of pulmonary hypertension (PH) as well as right heart hypertrophy in vivo and even reversed established vascular remodeling and PH in various animal models. These effects were attributable to both inhibition of vascular proliferation and induction of apoptosis. Since this pathway is abundantly activated in human disease, p110α represents a central target in PH.

Endoscopic Surveillance in Idiopathic Achalasia.

Idiopathic achalasia is a rare esophageal dysmotility disorder of unknown etiology with only palliative treatment available. Many studies have established a significantly increased risk of esophageal cancer in patients with achalasia. However, current guidelines advise against routine surveillance due to low absolute risk and a paucity of high-quality evidence and cost-effectiveness assessments. This review aims to assess the need for routine endoscopic surveillance in achalasia based on a growing body of literature calling in support of it, mainly due to the increased risk of esophageal cancer. We searched PubMed and Google Scholar electronic databases for articles within the last 10 years using the keywords 'achalasia', 'cancer,' 'neoplasms,' 'screening,' and 'surveillance.' After excluding pseudoachalasia/secondary achalasia, other esophageal dysmotility disorders, and associations with malignancies outside the esophagus, we selected 31 articles for this review. Through these articles, we identified areas of focus for ongoing and future research that may result in significant risk reduction of complications, including esophageal cancer and beyond.

Role of Gut Microbiota Dysbiosis in Breast Cancer and Novel Approaches in Prevention, Diagnosis, and Treatment.

Breast cancer is the most common cause of cancer-related deaths in women. Breast cancer is still a major cause of morbidity and mortality among women despite all the available diagnostic and treatment modalities. The gut microbiota has drawn keen interest as an additional environmental risk factor in breast cancer, especially in sporadic cases. This article explores factors that disrupt the normal gut microbial composition and the role of gut microbial dysbiosis in the development of breast cancer. We finalized 40 relevant articles after searching Pubmed and Google Scholar using regular keywords and the Medical Subject Headings (MeSH) strategy. Gut microbiota dysbiosis has been shown to play a role in the development of breast cancer via estrogen-dependent mechanisms and non-estrogen-dependent mechanisms involving the production of microbial-derived metabolites, immune regulation, and effects on DNA. The gut microbiota influence estrogen metabolism hence estrogen levels. The metabolites that have demonstrated anticancer properties include lithocholic acid, butyrate, and cadaverine. New approaches targeting the gut microbiota have come up and may yield new advances in the prevention, diagnosis, and treatment of breast cancer. They include the use of prebiotics, probiotics, and hormone supplements to restore normobiosis in the prevention and treatment of breast cancer.

An Exploration of the Effects of Radiofrequency Radiation Emitted by Mobile Phones and Extremely Low Frequency Radiation on Thyroid Hormones and Thyroid Gland Histopathology.

The use of mobile phones has widely increased over the last two decades. Mobile phones produce a radiofrequency electromagnetic field (RF-EMF), a form of non-ionizing radiation. In contrast to the ionizing radiation proven to cause DNA damage, the harmful effects of non-ionizing radiation on the human body have not been discovered yet. The thyroid gland is among the most susceptible organs to mobile phone radiation due to its location in the anterior neck. Our purpose in this literature review is to explore the effects of the electromagnetic field (EMF), especially radiofrequency emitted from mobile phones, on thyroid hormones and thyroid gland histopathology. We searched PubMed and Google Scholar databases for relevant studies published after the year 2000, using the following keywords: 'cell phones', 'mobile phones', 'telephones', 'electromagnetic fields', 'radiofrequency radiation', 'microwaves', 'thyroid gland', 'thyroid hormones', and 'thyroid cancer'. Our review revealed that mobile phone radiofrequency radiation (RFR) might be associated with thyroid gland insufficiency and alterations in serum thyroid hormone levels, with a possible disruption in the hypothalamic-pituitary-thyroid axis. The review also showed histopathological changes in the thyroid gland follicles after exposure of rats to non-ionizing radiation. The results were directly related to the amount and duration of exposure to EMF radiation. Further human studies exploring thyroid gland hormones, microscopic morphology, and thyroid cancer are highly recommended for future researches.

Participant-level characteristics differ by recruitment setting when evaluating a behavioral intervention targeting adolescents with asthma.

OBJECTIVE: The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors. METHODS: The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control). RESULTS: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001). CONCLUSION: Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

Measuring the Adhesion Forces for the Multivalent Binding of Vancomycin-Conjugated Dendrimer to Bacterial Cell-Wall Peptide.

Multivalent ligand-receptor interaction provides the fundamental basis for the hypothetical notion that high binding avidity relates to the strong force of adhesion. Despite its increasing importance in the design of targeted nanoconjugates, an understanding of the physical forces underlying the multivalent interaction remains a subject of urgent investigation. In this study, we designed three vancomycin (Van)-conjugated dendrimers G5(Van) n ( n = mean valency = 0, 1, 4) for bacterial targeting with generation 5 (G5) poly(amidoamine) dendrimer as a multivalent scaffold and evaluated both their binding avidity and physical force of adhesion to a bacterial model surface by employing surface plasmon resonance (SPR) spectroscopy and atomic force microscopy. The SPR experiment for these conjugates was performed in a biosensor chip surface immobilized with a bacterial cell-wall peptide Lys-d-Ala-d-Ala. Of these, G5(Van)4 bound most tightly with a KD of 0.34 nM, which represents an increase in avidity by 2 or 3 orders of magnitude relative to a monovalent conjugate G5(Van)1 or free vancomycin, respectively. By single-molecule force spectroscopy, we measured the adhesion force between G5(Van) n and the same cell-wall peptide immobilized on the surface. The distribution of adhesion forces increased in proportion to vancomycin valency with the mean force of 134 pN at n = 4 greater than 96 pN at n = 1 at a loading rate of 5200 pN/s. In summary, our results are strongly supportive of the positive correlation between the avidity and adhesion force in the multivalent interaction of vancomycin nanoconjugates.

Oritavancin Retains a High Affinity for a Vancomycin-Resistant Cell-Wall Precursor via Its Bivalent Motifs of Interaction.

Despite its potent antibacterial activities against drug-resistant Gram-positive pathogens, oritavancin remains partially understood with respect to its primary mode of hydrogen bond interaction with a cell-wall peptide regarding the role of its lipophilic 4'-chlorobiphenyl moiety. Here we report a surface plasmon resonance (SPR) study performed in two cell-wall model surfaces, each prepared by immobilization with a vancomycin-susceptible Lys-d-Ala-d-Ala or vancomycin-resistant Lys-d-Ala-d-Lac peptide. Analysis of binding kinetics performed on the peptide surface showed that oritavancin bound ∼100-1000-fold more tightly than vancomycin on each model surface. Ligand competition experiments conducted by SPR and fluorescence spectroscopy provided evidence that such affinity enhancement can be attributed to its 4'-chlorobiphenyl moiety, possibly through a hydrophobic interaction that led to a gain of free energy with a contribution from enthalpy as suggested by a variable-temperature SPR experiment. On the basis of these findings, we propose a model for the bivalent motifs of interaction of oritavancin with cell-wall peptides, by which the drug molecule can retain a strong interaction even with the vancomycin-resistant peptide. In summary, this study advances our understanding of oritavancin and offers new insight into the significance of bivalent motifs in the design of glycopeptide antibiotics.

Breast Milk Transforming Growth Factor ß Is Associated With Neonatal Gut Microbial Composition.

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers.

BACKGROUND & AIMS: A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS: We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS: Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS: Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.

Association of the autoimmune disease scleroderma with an immunologic response to cancer.

Autoimmune diseases are thought to be initiated by exposures to foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies to a limited group of autoantigens, including RPC1, encoded by the POLR3A gene. As patients with scleroderma and antibodies against RPC1 are at increased risk for cancer, we hypothesized that the "foreign" antigens in this autoimmune disease are encoded by somatically mutated genes in the patients' incipient cancers. Studying cancers from scleroderma patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to RPC1 but not in eight patients without antibodies to RPC1. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations triggered cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma and provide support for the idea that acquired immunity helps to control naturally occurring cancers.

Exomic analysis of myxoid liposarcomas, synovial sarcomas, and osteosarcomas.

Bone and soft tissue sarcomas are a group of histologically heterogeneous and relatively uncommon tumors. To explore their genetic origins, we sequenced the exomes of 13 osteosarcomas, eight myxoid liposarcomas (MLPS), and seven synovial sarcomas (SYN). These tumors had few genetic alterations (median of 10.8). Nevertheless, clear examples of driver gene mutations were observed, including canonical mutations in TP53, PIK3CA, SETD2, AKT1, and subclonal mutation in FBXW7. Of particular interest were mutations in H3F3A, encoding the variant histone H3.3. Mutations in this gene have only been previously observed in gliomas. Loss of heterozygosity of exomic regions was extensive in osteosarcomas but rare in SYN and MLPS. These results provide intriguing nucleotide-level information on these relatively uncommon neoplasms and highlight pathways that help explain their pathogenesis.

Evaluation of a web-based asthma management intervention program for urban teenagers: reaching the hard to reach.

PURPOSE: Asthma interventions targeting urban adolescents are rare, despite a great need. Motivating adolescents to achieve better self-management of asthma is challenging, and the literature suggests that certain subgroups are more resistant than others. We conducted a school-based, randomized controlled trial (RCT) to evaluate Puff City, a Web-based, tailored asthma intervention, which included a referral coordinator, and incorporated theory-based strategies to target urban teens with characteristics previously found to be associated with lack of behavior change. METHODS: To identify eligible teens, we administered questionnaires on asthma diagnoses and symptoms to ninth through 12th graders of participating schools during a scheduled English class. We randomized eligible, consenting students to Puff City (treatment) or generic asthma education (control). RESULTS: We randomized 422 students (98% African-American, mean age = 15.6 years). At 12-month follow-up, adjusted odds ratios (aORs) (95% confidence intervals) indicated intervention benefit for treatment teens for symptom-days and restricted activity days (analyzed as categorical variables) as aOR = .49 (.24-.79), p = .006 and .53 (.32-.86), p = .010, respectively. Among teens meeting baseline criteria for rebelliousness, treatment teens reported fewer symptom-days, symptom-nights, school absences, and restricted activity days: aOR = .30 (.11-.80), .29 (.14-.64), .40 (.20-.78), and .23 (.10-.55); all p < .05. Among teens reporting low perceived emotional support, treatment students reported only fewer symptom-days than controls: aOR = .23 (.06-.88), p = .031. We did not observe statistically significant differences in medical care use. CONCLUSIONS: Results suggest that a theory-based, tailored approach, with a referral coordinator, can improve asthma management in urban teens. Puff City represents a viable strategy for disseminating an effective intervention to high-risk and hard-to-reach populations.

Determination of serum aldosterone by liquid chromatography and tandem mass spectrometry: a liquid-liquid extraction method for the ABSCIEX API-5000 mass spectrometry system.

AIMS: Accurate serum aldosterone determination is critical to the screening and diagnosis of primary aldosteronism, the localisation of aldosterone producing tumours, and the investigation of other disorders of the renin-angiotensin system. Mass spectrometry offers a means to overcome problems with method-dependent bias between competitive immunoassays for aldosterone. The authors have developed a simple, sensitive and precise liquid-liquid extraction aldosterone method for the ABSCIEX API-5000 liquid chromatography and tandem mass spectrometry (LC-MS/MS) system. METHODS: Using d7-aldosterone internal standard, 500 µl of sample is extracted with 2500 µl of methyl tertbutyl ether followed by dry-down, reconstitution and LC-MS/MS analysis in ESI negative mode. Method validation was undertaken using standard approaches and comparison made against a commercial radioimmunoassay. Accuracy was assessed using EQA material with assigned aldosterone concentrations. RESULTS: The assay was linear up to 3420 pmol/l (LOQ=50 pmol/l, LOD<22 pmol/l). Total CVs were ≤5% for concentrations ≥120 pmol/l and 10% at the LOQ. Mean accuracy was 98.5% against GCMS assigned material. CONCLUSION: The authors present a precise, sensitive and simple aldosterone method suitable for routine clinical use that requires no solid phase extraction or specialised ion sources.

γ2-Melanocyte stimulation hormone (γ2-MSH) truncation studies results in the cautionary note that γ2-MSH is not selective for the mouse MC3R over the mouse MC5R.

The melanocortin system has been implicated in a multitude of physiological pathways including obesity, satiety, energy homeostasis, sexual behavior, pigmentation, sodium regulation, hypertension, and many others. Based upon studies of the endogenous melanocortin receptor agonists at the cloned human melanocortin receptor proteins, it was concluded that the γ-MSH related agonist ligands are selective for the MC3 versus the MC4 and MC5 receptors. In attempts to understand and identify the specific amino acids of γ2-MSH important for MC3R selectivity, we have performed N- and C-terminal truncation studies and pharmacologically characterized twenty-eight ligands at the mouse MC1 and MC3-5 melanocortin receptors. The C-terminal Trp-Asp9-Arg¹°-Phe¹¹ residues are important for nM potency at the mMC3R and the Arg7-Trp8 residues are important for mMC5R nM potency. We observed the unanticipated results that several of the C-terminal truncated analogs possessed nM agonist potency at the mMC3 and mMC5Rs which lead us to perform a comparative side-by-side study of the mouse and human MC5R. These data resulted in µM γ2-MSH analog potency at the hMC5R, consistent with previous reports, however at the mMC5R, nM γ2-MSH analog potency was observed. Thus, these data support the hypothesis of important species specific differences in γ-MSH related ligand potency at the rodent versus human MC5R subtype that is critical for the interpretation of in vivo rodent physiological studies. These results prompted us to examine the affects of a peripherally administered melanocortin agonist on hypothalamic gene expression levels of the MC3R, MC4R, and MC5R. The super potent non-selective NDP-MSH agonist was administered i.p. and resulted in significantly decreased levels of mMC3R and mMC5R hypothalamic mRNA versus saline control. These data provide for the first time data demonstrating peripherally administered NDP-MSH can modify hypothalamic melanocortin receptor expression levels.